OR19
Immunotherapy with RUTI vaccine, a new universal tool to improve the chemotherapy in active tuberculosis
P Soldevilla(2,3,4) A Buisan(5) S Saladrigas(5) L Arias(4) A Jimenez-Melsió(5) C Vilaplana(2,4) M Amat(5) P J Cardona(1,2,3,4)
1:Microbiology Department. Hospital Universitari Germans Trias i Pujol. IGTP; 2:Centro de Investigación Biomédica en Red de Enfermedades Respiratorias (CIBERES); 3:Department of Genetics and Microbiology. Universitat Autònoma de Barcelona; 4:Experimental Tuberculosis Unit. Institut Germans Trias i Pujol. Badalona; 5:Archivel Farma, s.l., Badalona
RUTI is a vaccine made with liposomed fragments of Mycobacterium tuberculosis (Mtb) already tested in several clinical trials in patients with latent tuberculosis infection. The main objective of the assay was to test, in an active TB murine model, whether the immunotherapy with RUTI, alone or combined with chemotherapy at the onset of the disease, would be therapeutic and safe. Active TB murine experimental model has been tested, in C3HeB/FeJ mouse strain, including both sexes. Animals were infected intravenously with 4.04 E+04 CFU of Mtb H37Rv. After development of active TB (w5), experimental groups included subcutaneous administration of RUTI combined or not with oral administration of chemotherapy (RHZE). Treatment was well tolerated, and animals were euthanized to determine the bacillary load, damage in lungs and determinate T-cell response against PPD, ESAT-6, Hsp16-3 and PsTS1 though ELISPOT in splenocytes. The administration of RUTI alone reduced -1.5 log10 the bacillary load and synergized with chemotherapy (-2.5 log10 reduction) one week after its inoculation, decreasing the lung pathology. The therapeutic effect might be related to the increase of the T-cell response against PsTS1 and HSP16.3 when treating with RUTI plus chemotherapy. This data encourages the administration of RUTI at the beginning of TB chemotherapy, for a faster reduction of the bacillary load and to explore a shorter drug treatment length. A clinical trial (CONSTAN) has been recently approved by the Spanish Agency for Medicines and Health Products (AEMPS) to confirm this finding.